This proposal outlines a program of research designed to achieve a greater understanding of the chemistry of technetium. It is hoped that the knowledge gained will aid substantially in the design of future radiopharmaceuticals incorporating the radionuclide 99mTc for use in diagnostic nuclear medicine. Emphasis will be placed on the preparation and isolation of technetium complexes in different oxidation states and the establishment of their chemical compositions, electronic properties and stereochemistry using methods which have been successfully applied to the coordination chemistry of other transition metals. In order to prepare isolatable amounts of technetium complexes, use will be made of the long-lived radionuclide 99Tc (t1/2 2.12 x 10 to the 5th power yr.). After preparing known compounds of the element in defined oxidation states as precursors, modern synthetic methods will be employed for controlled ligand substitution reactions to make a variety of compounds, principally in oxidation states III, IV, V and VI. As the synthetic program proceeds, a systematic collection of magnetic and spectral data as well as polarographic and cyclic voltammetric studies will be made to provide a profile of oxidation state, stereochemistry, nature of the bonding and relative ligand affinities of technetium compounds. This information will be obtained by magnetic susceptibility measurements and by application of nuclear magnetic resonance, electron paramagnetic resonance, and ESCA and electronic (UV-VIS) spectroscopy. As the systematics of the element's behavior emerge, studies will be initiated of the chemistry of suitable technetium complexes with amino acids and small polypeptides. These materials will furnish all of the binding sites found in the higher molecular weight proteins. Particular emphasis will be placed on electron donor groups, which will be examined individually and in combination to investigate the properties of the ligating sites as a function of technetium oxidation state.